The determination of the blood glucose concentration, and the corresponding medication is an essential item of the daily routine of diabetics. In this case, the blood glucose concentration needs to be determined quickly and easily several times a day, typically 2 to 7 times, in order to be able to take appropriate medical measures when relevant. In many instances, a modification is performed in this process by means of automatic systems, in particular with the aid of insulin pumps.
In order not to restrict the daily routine of the diabetic more than is absolutely necessary, use is frequently made of appropriately mobile units that should be easy to transport and to handle so that the blood glucose concentration can be measured without any problem, for example at the workplace or during free time.
There are currently available various mobile units that function in part according to different measuring methods and with the use of different diagnostic methods. A first measuring method is based, for example, on an electrochemical measuring method in which a blood sample that is taken from the body tissue of the patient by perforating a skin layer by means of a lancet is applied to an electrode coated with enzymes and mediators. Corresponding test strips for such electrochemical measuring methods are described, for example, in U.S. Pat. No. 5,286,362, the disclosure of which is hereby incorporated herein by reference in its entirety. Other known measuring methods use optical measuring methods that are based, for example, on the fact that the substance (analyte) to be detected can react with specific detection reagents, a change in color of the reaction mixture occurring in the process. Systems for detecting such color reactions and thus for detecting the corresponding analytes are known, for example from CA 2,050,677, the disclosure of which is hereby incorporated herein by reference in its entirety.
The detection methods described are overwhelmingly based on the fact that a patient firstly takes an appropriate sample of the body fluid to be examined, this possibly being both a blood sample and a urine sample, this then being examined appropriately by means of the test apparatus. This method includes various disadvantages, however. Thus, this method is firstly extremely complicated and presupposes a number of handling steps. Thus, for example, a lancet needs to be provided and loaded, subsequently a skin layer must be perforated by means of this lancet, and then a blood drop thus produced must be applied to a test strip, and this test strip needs to be evaluated subsequently by means of an appropriate unit. For many patients, in particular older people and children, these handling steps can frequently be carried out only with difficulty, since the patients have restricted motor ability and limited eyesight, for example. Furthermore, these method steps can be carried out discretely only in a few instances so that, for example, protection of the privacy of the patient during a measurement at the workplace is only insufficiently preserved. Again, faulty operation in the course of the measuring method can easily lead to wrong measured values accompanied, in part, by fatal consequences of a false medication built on wrong measurement results.
For this reason, there are known from the prior art systems that generate continuously measured data and that can be used as an alternative or in addition to the above-described systems or methods, for example in order to reduce the number of individual measuring operations. Thus, for example, systems are commercially available that comprise a membrane tube in the subcutaneous tissue through which a transport liquid is pumped. Via the membrane, glucose diffuses into the transport liquid, which is then in turn conveyed to an electrochemical measuring cell. The glucose concentration is then measured in the electrochemical measuring cell. However, there is the disadvantage with such an arrangement for continuously producing measured values that it requires the patient to always carry along a supply of transport liquid and an appropriate waste container for holding contaminated transport liquid.
Further sensor types, known from the prior art, for continuously producing measured values are configured to be implanted in a body tissue; for example, U.S. Pat. No. 6,892,085 B2, the disclosure of which is hereby incorporated herein by reference in its entirety. Generally, such continuous monitoring set ups comprise an encapsulated glucose sensor system that comprises a glucose sensor and a protective capsule. In this case, three electrodes, a working electrode, a counter electrode and a reference electrode are provided that are applied to one side of a substrate. To improve implantability, this electrode arrangement can be integrated in a hollow needle that is used as an insertion aid to puncture body tissue. After the insertion, the hollow needles are withdrawn from the tissue again and only the sensors remain in the body tissue. Other exemplary systems are described, e.g., in U.S. Pat. No. 5,591,139, the disclosure of which is hereby incorporated herein by reference in its entirety.
A main advantage of the continuously measuring systems is that it is also possible to detect relatively short periodic fluctuations in the glucose concentration (time profiles) in conjunction with the intake of food and physical exercise. This is of great significance for “setting” of a diabetic.
The implantable sensors known from the prior art are, however, extremely complicated with regard to their design and production. If it is presupposed that these sensors are disposable sensors that can be used only for a short time (typically approximately one week), it then becomes clear that the methods used in the case of the sensors known from the prior art do not meet the requirements placed on disposable articles. Thus, for example, a complicated micro-structuring method, in particular a lithographic method, is required to produce the sensor known from U.S. Pat. No. 5,591,139. However, such methods cannot be combined with the production of cost-effective disposable articles. Again, complicated structuring methods are required to produce the sensor known from U.S. Pat. No. 6,892,085 B2, since the electrode pads must be structured carefully. In view of the small size of these electrodes, lithographic methods are likewise required therefor, and this in turn drives up the costs for producing such sensors.
Again, lithographic methods, in particular the etching of metal layers associated with these methods, are not always as reliable as is required for producing medical products. In particular, it can occur from time to time that individual electrodes are still interconnected by “bridges” or webs such that the functionality of the sensors can be slightly impaired or even completely negated, because of production problems. A further disadvantage of the sensors known from the prior art, such as are apparent from U.S. Pat. No. 6,892,085 B2 and U.S. Pat. No. 5,591,139, for example, consists in the use of a hollow needle or in the use of a capillary.
Instead of the previously described implantable sensors, in the case of which micro-structuring methods are used to structure the electrode pads, for example a lithographic method, implantable sensors, for example those known from WO 90/10861, the disclosure of which is hereby incorporated herein by reference in its entirety, can be formed in a wire-shaped fashion. That is, individual wires can be embedded in an isolating mass. The active measuring surfaces are respectively the end faces of the wires inside a plane that is exposed by a separating operation or the like. Such sensor systems are capable of multiple use, and can be used in an appropriate measuring instrument. The sample is applied inside the measuring instrument to the previously exposed end faces of the wires (in vitro measurement). Another example of systems employing wire-shaped sensors is disclosed in U.S. Pat. No. 4,805,624, the disclosure of which is hereby incorporated herein by reference in its entirety.
The above-discussed solutions in accordance with the prior art make contact with a body tissue only in a very restricted area. The electrode arrangement, usually comprising a working electrode, a counter electrode and a reference electrode, is very restricted locally, that is to say is capable of recording informative results only in a very small area of the body tissue. The functioning of the sensors known from the prior art, which can also be implanted, can be disturbed by local tissue inhomogeneities such as, for example, wound effects or fat deposits. Furthermore, sensor membrane characteristics can have a negative effect on the measured values. The electrode pads from other known systems have electrodes which lie next to one another in one plane and in the case of which the required miniaturizability is substantially restricted as a function of the selected micro-structuring methods. The disadvantage of the sensors known from the prior art, which can also be implanted, is to be seen in that it is impossible to make use of cost-effective production methods that are required for large batch production and could be used in the course of mass production.